Hyaluronan fragments act as an endogenous danger signal by engaging TLR2

Kara A. Scheibner, Michael A. Lutz, Sada Boodoo, Matthew J. Fenton, Jonathan D. Powell, Maureen R. Horton

Research output: Contribution to journalArticlepeer-review

Abstract

Upon tissue imjary, high m.w. hyaluronan (HA), a ubiquitously distributed extracellular matrix component, is broken down into lower m.w. (LMW) fragments, which in turn activate an innate immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-, TNFR-associated factor-6-, protein kinase Cζ-, and NF-κB-dependent pathway. Furthermore, we show that intact high m.w. HA can inhibit TLR-2 signaling. Finally, we demonstrate that LMW HA can act as an adjuvant promoting Ag-specific T cell responses in vivo in wild-type but not TLR-2null mice.

Original languageEnglish (US)
Pages (from-to)1272-1281
Number of pages10
JournalJournal of Immunology
Volume177
Issue number2
DOIs
StatePublished - Jul 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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